The goal of this research is to develop methods to predict with chemical accuracy the stereoselectivities of organic reactions, with initial concentration on three extraordinarily valuable synthetic procedures which are critical steps in the natural product synthesis, particularly for antibiotic ionophores such as monensin and rifamycin S. The reactions to be studied are (1) hydroborations and (2) epoxidations of chiral or prochiral alkenes, and (3) carbonyl additions and aldol-type condensations which produce one or more chiral centers. The research will utilize state of the art ab initio quantum mechanical calculations to determine the transition state structures of moderately small, but chemically accessible, model reactions. Lower level, but still semi-quantitatively reliable, calculations will be used to probe the influence of substituent stereochemistry on the stereochemistry of bond formation in each of these reactions. New stereochemical predictions will be tested experimentally. Investigations of the influence of stereochemically rigid systems (e.g., cycloalkenes and bicycloalkenes) upon stereochemistries and rates of addition reactions will also be carried out. For example, the differences in rates of additions to norbornenes vs. bicyclooctenes, cyclohexenes vs. cyclopentenes and cis and trans alkenes are most likely explicable in terms of the stereochemistries of allylic bonds relative to the Pi bonds.